Genetic control of immunity to helminth infections

Immune responses to infections with par~zsitic worms show well defined genetic control. In man, domestic animai~ and experimental rodents, the level and na:ture of these responses may differ markedly between individuals or be- tween breeds and strains, and be reflected in the overall outcome of the infection in terms of resis- tance, susceptibility and pathology. A basic tenet of evolutionary biology is that populations embrace a substantial degree of genetic diversity upon which natural selection can act to maximize the fitness of particular populations within particular en- vironments. An important element of such diversity is seen in the differing abilities of individuals to cope with infectious diseases, an element which par~,sitologists have rec- ognized much later th~xl their colleagues in virology, bacteriology and plant pathology. (Genetic diversity wiflfin parasite popula- tions probably has equal significance in the context of the evolulJLon and stability of host-parasite relationslfips but will not be considered here.) Although the existence of host variation in respo~Lse to helminth infec- tions has been recorded empirically for some time, the systematic exploration and exploitation of this phenomenon is com- paratively recent. It is now widely recog- nized that a substantial part of this variation has its origins in differential immune re- sponsiveness to infection and is genetically determined. Progress in understanding the genetic control of variation has gone hand- in-hand with analysis of the immunological mechanisms involved; indeed the two pro- vide reciprocally fruit_tiff fields of research 1. Inevitably attention has concentrated largely upon the genetic control of resis- tance elicited by infection or by vaccination, but immunosuppressive and im- munopathological phenomena have also been examined. Much of the work has been carried out in experimental systems using laboratory rodents and particularly the mouse, for which a wide variety of defmed strains is available (Table 1). Important studies have also been made in domestic ani- mals and in man. The extent of the variation of responses to infection that can occur can be illustrated by reference to the nematode Trichinella spiralis in the mouse, an experimental system which has been studied in greater detail than any other (Table 2). Variation exists in almost every parameter that has been moni- tored, but it is important to note that, as far as the infection itself is concerned, variation is essentially quantitative, not qualitative. All strains of mice so far tested (excluding mutant strains) terminate the intestinal phase of infection by means of an immune response, although some take considerably longer than others to do so and may, in con- sequence, acquire heavier burdens of larvae in the muscles. Qualitative variation has been recorded in other systems, for example individuals of certain mouse strains appear completely incapable of controlling infec- tion with Trichuris muris 3.